User:James D Watson/Proteins Intro

Introduction to proteins
This is an example private page that could be used in teaching. I will copy some of the info from the 5p21 page and use it here to expand details and bring in other aspects like structural superpositions.

5p21 Overview
The crystal structure of the H-ras oncogene protein p21 complexed to the slowly hydrolysing GTP analogue GppNp has been determined at 1.35 A resolution. 211 water molecules have been built into the electron density. The structure has been refined to a final R-factor of 19.8% for all data between 6 A and 1.35 A. The binding sites of the nucleotide and the magnesium ion are revealed in high detail and consists of a characteristic Walker motif (GXXXXGK[T/S]). For the stretch of amino acid residues 61-65, the temperature factors of backbone atoms are four times the average value of 16.1 A2 due to the multiple conformations. In one of these conformations, the side chain of Gln61 makes contact with a water molecule, which is perfectly placed to be the nucleophile attacking the gamma-phosphate of GTP. Based on this observation, we propose a mechanism for GTP hydrolysis involving mainly Gln61 and Glu63 as activating species for in-line attack of water. Nucleophilic displacement is facilitated by hydrogen bonds from residues Thr35, Gly60 and Lys16. A mechanism for rate enhancement by GAP is also proposed.

About this Structure
5P21 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference
Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis., Pai EF, Krengel U, Petsko GA, Goody RS, Kabsch W, Wittinghofer A, EMBO J. 1990 Aug;9(8):2351-9.

Structural superposition
The viewer below left shows the structural superposition of the triphosphate conformation of H-ras p21 (PDB entry 5p21 - coloured orange) with Gdp-bound human rab21 gtpase (PDB entry 1z0i - coloured blue), the structural superposition was made using the MSDfold(SSM)1 server at the EBI2. Note that the global fold of these two proteins is almost identical yet their sequence identity is only 29.6% (as determined using FASTA). The viewer below right shows the p-loops of both structures superposed. The ligands bound superpose particularly well and comparison of the two p-loops loops show significant structural similarity but also highlights the sequence differences between the two proteins.  